Basics

Definitions

Tissue: An essemble of similar cells and their extracellular matrix (organisational level between an organ and a cell).

Enhancers are associated with chromatin modifications that are distinct epigenetic features in a tissue-specific manner.

Once you’ve identified a genetic variant you need to see what gene that variant is effecting and in what tissue type. E.g. the T2D-associated genetic variant may lie within an active enhancer in pancreatic islets (regions of the pancreas containing hormone-producing cells) ¹ ²
Note only ~0.1% of the genome is variable (just 3 million bases).

Pathophysiology: In this context, how a mutation affects protein function which affects disease.

Additive genetic effects: Two or more genes source a single contribution to the final phenotype or two alleles of a single gene (in a heterozygote) combine so that their combined effects equal the sum of their individual effects.

Non-additive genetic effects: Examples include dominance (of alleles at a single locus) or epistasis (effect of a gene is dependent on other genes, e.g. effect of one gene is suppressed/masked by a different gene).

UK biobank

Started recruiting patients in 2006.
Data on 500,000 individuals (imaging/ genotype/ whole exome sequencing/ blood etc).
Currently conducing whole genome sequencing on 50,000 individuals, then hope to do all 500,000.

UK10K

Started in 2008.
For rare genetic variants.
Generate whole genome and exome sequence data for almost 10,000 highly phenotyped individuals.
Hopes to be able to detect variants with allele frequencies as low as 0.1%!

100,000 Genomes Project

Started in 2012/13.
Sequenced 100,000 genomes from 85,000 people with rare diseases or cancer and their families.

GTEx

Investigate variation in gene expression across people.
Samples from 53 non-diseased tissues from 1000 people.
Help to identify what tissues and genes genetic variants are effecting.

ENCODE

Encyclopedia of DNA elements.
Develop a list of functional elements in the human genome, including regulatory elements.